Segmental Hair Analysis of Diphenhydramine and Cyclizine Following a Single Dose

Diphenhydramine and cyclizine are over-the-counter (in many countries) antihistamines that have considerable sedative effects. Therefore, they can be used in drug-facilitated crimes to incapacitate victims. There is a knowledge gap regarding detection possibilities and concentration levels of these antihistamines in hair. This study aimed to investigate whether a single dose of diphenhydramine and cyclizine could be quantified in head hair, and for how long. A single-dose study was conducted in which 12 adult volunteers ingested a single dose of diphenhydramine (25 mg) and cyclizine (44 mg). Hair samples were collected before drug intake and at 1, 3, 5, and if possible, 12 months after intake. To quantify a single dose of antihistamines in head hair, a validated LC-MS/MS method with a lower limit of quantification of 1 pg/mg was applied. Both antihistamines and their main metabolites, N-demethyldiphenhydramine and norcyclizine, were detected in all hair samples collected up to 5 months after intake. Twelve months after intake, diphenhydramine was quantifiable in 25% and cyclizine in 62.5% of available hair samples. The concentrations found in hair within 1 year after intake ranged from 0 to 610 pg/mg for diphenhydramine and from 0 to 590 pg/mg for cyclizine. The median decrease in concentration over 2, 4, and 11 months was 43%, 70%, and 100% for diphenhydramine and 40%, 64%, and 98% for cyclizine. The data obtained provided indicative concentration ranges for a single oral dose of diphenhydramine and cyclizine in hair, thereby improving the interpretation of hair analyses in forensic casework.